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D-Lactic Acidosis

Craig Petersen RD, CNSC

D-lactic acidosis, also referred to as D-lactate encephalopathy, is a rare neurological syndrome that can occur in individuals with short bowel syndrome (SBS) or following jejuno-ileal bypass surgery. A home parenteral or enteral nutrition (HPEN) consumer may develop the neurological symptoms—which can be quite striking—several months to years after the initial diagnosis of a malabsorption disorder.
Misdiagnosis of D-lactic acidosis is common, as the neurologic symptoms are sometimes attributed to other causes. With proper diagnosis, D-lactic acidosis can be treated promptly and the symptoms will usually resolve within several hours to a few days.

Symptoms

Neurological symptoms associated with this syndrome typically present after the ingestion of enteral formula or food high in carbohydrates (either simple or complex) and include altered mental status, slurred speech, confusion, disorientation, difficulty concentrating, memory deficits, excessive sleepiness, weakness, abnormal gait, problems with muscle coordination, and even coma. Individuals with D-lactic acidosis often appear to be inebriated, or drunk, though they may not have consumed alcohol and alcohol is not detected in the blood. Behavior during episodes of D-lactic acidosis can be aggressive, hostile, or abusive.
Neurological symptoms are episodic and may last from hours to days. They are accompanied by metabolic acidosis and elevation of plasma D-lactic acid (also referred to as D-lactate) concentration.

Cause

In D-lactic acidosis, carbohydrate that is not properly absorbed is fermented by an abnormal bacterial flora in the colon. This fermentation produces excessive amounts of D-lactate. High amounts of D-lactate are then absorbed into the circulatory system, resulting in elevated concentrations of D-lactate in the blood.
It has been thought that the neurologic symptoms are a result of this unusual D-lactate elevation, but it is unclear if this is actually the cause or whether other factors are responsible, as metabolic acidosis and elevation of blood D-lactate alone are not capable of producing these symptoms. Other factors may also play a role in the promotion of this neurological disorder, such as the generation of toxic substances or disturbances of metabolic pathways.
Regardless of the specific factors that ultimately cause D-lactic acidosis, there are certain conditions required for the development of this disorder. Foremost is the presence of a colon with a flora rich in D-lactate–producing bacteria, accompanied by the ingestion and malabsorption of relatively large amounts of carbohydrate that feeds these bacteria. Additionally, an impairment of D-lactate metabolism appears to play a necessary role.

Diagnosing D-lactic Acidosis

D-lactic acidosis should be considered when any person with SBS or other malabsorptive disorder presents with neurologic symptoms consistent with the syndrome, with no other causes identified. The literature indicates a colon must be present for the disorder to occur. The level of suspicion should be further raised if the consumer received recent antibiotic therapy or was started on probiotics, both of which could alter the intestinal flora to favor D-lactate production. A consumer or caregiver may not report initial episodes of altered neurological status, depending on how severe they are and how long they last. However, earlier reporting of neurologic symptoms may lead to earlier diagnosis.
Because of the transient or episodic nature of D-lactic acidosis, laboratory confirmation of the syndrome can sometimes present a challenge. Individuals with D-lactic acidosis often report a history of previous neurologic symptoms similar in nature to those occurring in the current episode. A diet history will frequently reveal the ingestion of relatively large amounts of carbohydrate in the form of simple sugars before the onset of symptoms. Some investigators have confirmed the diagnosis by administering an oral carbohydrate challenge, which reproduced neurologic symptoms and significantly increased the serum D-lactate concentration.
Laboratory analysis will typically reveal a metabolic acidosis. Normal laboratory analysis may reveal elevated serum lactate, but frequently they show normal. Because routine blood tests are designed to only assay for L-lactate, it is essential that a specific request for D-lactate levels is ordered to determine plasma D-lactate concentration. At this time, the blood sample needs to be sent out to Mayo Clinic, since other labs do not ordinarily perform this test. Additionally, D-lactate levels need to be obtained during the period of neurologic disturbance, as levels decline rapidly upon resolution of the symptoms. Frequently, the failure to properly obtain blood D-lactate levels delays or obscures diagnosis. Although there is not complete consensus, a plasma D-lactate concentration of 3 mmol/L is frequently used in defining D-lactic acidosis.
The clinical or biochemical information leading to the suspicion of D-lactic acidosis is frequently confirmed or supported by the response to treatment. Appropriate treatment often results in rapid resolution of neurologic symptoms and prevents or reduces further recurrence of the syndrome.

Acute Treatment

Appropriate treatment of D-lactic acidosis depends on the person’s clinical status. During an acute episode, withholding enteral (oral or tube feeding) intake of carbohydrate will remove the primary source of further D-lactate production. Carbohydrates should be provided by parenteral (IV) route only, until adequate recovery from neurologic symptoms has been achieved.
IV bicarbonate and rehydration fluids can be administered to correct the acidosis. Assuring adequate hydration will optimize the kidneys’ ability to excrete D-lactate. Lactated Ringer’s solutions should be avoided because they contain D-lactate. Thiamin can be given intravenously to assure that adequate amounts are available for metabolism of pyruvate, which could be involved in the symptoms.
Oral antibiotic therapy can be initiated to hasten a change in the intestinal flora to one with fewer D-lactate–producing bacteria. This will allow a more rapid reintroduction of appropriate sources and amounts of carbohydrate back into the diet, when recovery from the neurological episode is complete.
Oral antibiotics that are poorly absorbed and active against acid-resistant bacteria such as clindamycin, tetracycline, metronidazole, neomycin, vancomycin, and kanamycin are most effective for eradicating the offending bacteria. In adults, the recommended antibiotic regimens include clindamycin 300 mg three times per day, vancomycin 125 mg four times per day, neomycin 500 mg three times per day, and tetracycline 500 mg three times per day. However, the length of antibiotic therapy required varies from person to person and within the same person from one episode to another.
Treatment of acute episodes of D-lactic acidosis with carbohydrate restriction (both simple and complex), rehydration, and administration of antibiotics typically results in resolution of neurologic symptoms within hours to a few days.

Long-term Treatment

Once the consumer has recovered from the acute episode of D-lactic acidosis, a chronic treatment regimen should be designed to limit or prevent future occurrences. Long-term management should focus on efforts to limit oral or enteral carbohydrate intake; limit dietary sources of D-lactate; promote and maintain a bowel flora predominated by bacteria that do not produce D-lactate; support metabolism of D-lactate; and when necessary, consider surgery to alter any anatomical contributions to the disorder. The success of each individual treatment will largely determine the extent to which other interventions are required.

Avoid Simple Sugars, D-Lactate

In some cases, all that may be required to avoid D-lactic acidosis is restriction of dietary carbohydrates, particularly simple sugars. A dietitian can review sources of simple sugars to help with diet modification. Simple sugars are metabolized to D-lactate more rapidly than more complex carbohydrates and probably generate more D-lactate. Without an adequate source of carbohydrate, the intestinal bacteria are unable to produce enough D-lactate to precipitate an episode of D-lactate encephalopathy.
To avoid adding to an already high D-lactate load in those with a history of D-lactic acidosis, it is prudent to avoid intake of foods containing high amounts of D-lactate also. Some fermented foods are rich in D-lactate, including yogurt, sauerkraut, and pickled vegetables and should not be eaten.

Hydration Helps

While maintaining adequate hydration optimizes excretion of D-lactate by the kidneys, good hydration status is also important in reducing risk of kidney stones and maintaining good kidney function. Many consumers with SBS are chronically dehydrated, due to excessive gastrointestinal fluid losses. The usual dietary modifications to reduce stool output should be followed (see resources at www.oley.org).
When oral rehydration solutions are used, they should contain only modest amounts of carbohydrate. If the consumer is unable to achieve adequate hydration by enteral route, then IV hydration may be necessary. Again, Lactated Ringer’s should be avoided due to the D-lactate contained in these solutions.
Other dietary interventions to be considered include those aimed at optimizing metabolism of D-lactate. Oxalate, which is found in the diet and absorbed in the colon, is a strong inhibitor of the enzyme that helps rid the body of D-lactic acid. Additionally, many people with SBS and a colon in continuity will eventually develop calcium oxalate kidney stones. Therefore, efforts should be undertaken to keep serum oxalate at low levels, which should help control serum D-lactate levels and reduce the risk of kidney stone formation.
Normally, very little oxalate is absorbed from the diet, with most oxalate in the serum and urine being produced from metabolism of ascorbic acid and amino acids. Ordinarily, dietary calcium binds to dietary oxalate, forming a complex that is too large to be absorbed by the intestine. However, in individuals with fat malabsorption, dietary calcium binds to the unabsorbed fat, leaving less calcium available to complex with dietary oxalate. The resulting free oxalate can then be absorbed in the colon, increasing serum oxalate levels and increasing risk of kidney stone formation. Therefore, a low-fat, low-oxalate diet should be considered by both those suffering from D-lactic acidosis and anyone with SBS and a colon, especially if high levels of oxalate are found in the urine.
Unfortunately, there is poor agreement regarding which foods are high in absorbable oxalate. Many published lists of high oxalate foods contradict one another. This often results in great confusion about which foods to possibly limit or avoid in the diet. Some recent research, actually measuring oxalate levels, has determined that ingestion of beets, spinach, rhubarb, nuts, peanuts, cashews, chocolate, strawberries, wheat bran, and tea can significantly raise blood and urine oxalate levels. The extent to which other foods can raise blood or urine oxalate levels is unclear.
In practical terms, both of these dietary restrictions can be difficult to achieve. An alternative is to supplement the diet with large amounts of calcium at each meal. Quantities of up to a gram of elemental calcium, in the form of a liquid or chewable supplement, can be given at each meal. This increases the amount of calcium available to complex with dietary oxalate, inhibiting oxalate absorption.
Supplementing large amounts of calcium may also help to increase the pH in the bowel, which could result in decreased D-lactate production by intestinal bacteria. Ascorbic acid (vitamin C) should be supplemented with caution, as it can be metabolized to oxalate. When dietary modifications are insufficient to prevent recurrence of D-lactic acidosis, more aggressive measures to favorably alter the intestinal flora should be used.

Role of Antibiotics, Probiotics

Long-term management of D-lactic acidosis often includes the use of oral antibiotics, in an effort to maintain an intestinal flora that is not predominated by D-lactate–producing bacteria. In some people with a history of D-lactic acidosis, a course of antibiotic therapy is initiated if that person develops the typical symptoms. In other cases of frequent repeated episodes of D-lactate encephalopathy, a continuous regimen of rotating antibiotics may be prescribed, in an attempt to achieve a more permanent suppression of bacteria that are D-lactate producers. These regimens sometimes include periodic brief antibiotic holidays to reduce the detrimental side effects of long-term antibiotic use.
It has been suggested that probiotics might be used as an alternative or adjunct to the use of antibiotic therapy for D-lactic acidosis. Probiotics are live bacteria cultures, which are taken orally for the purpose of altering the intestinal flora in a beneficial manner. At this point, the effectiveness of probiotics in the treatment of D-lactic acidosis is unclear. If probiotics are used in a treatment regimen, it is essential that the probiotic selected for treatment be known to be void of D-lactate–producing bacteria. The manufacturer should be contacted for this information, and if it is unavailable, use of that probiotic should be avoided.

Surgical Intervention

In cases where dietary and medical treatments are unsuccessful, surgical intervention may be considered. In consumers with SBS, surgeries to improve intestinal absorption, such as bowel tapering/intestinal lengthening or small bowel transplantation, may correct the problem. Although an extreme measure, removal of the colon might be considered in select individuals in whom the disability from the D-lactate encephalopathy is so devastating that the potential benefits outweigh the adverse consequences of a colectomy.

Cautions

Consumers should avoid driving and other similar activities during episodes or impending episodes of D-lactic acidosis. They should keep a letter from their doctor describing D-lactic acidosis and its diagnosis and treatment close at hand, to provide information during episodes of encephalopathy. This can facilitate prompt and appropriate medical treatment, rather than a side trip to the local detention facility for apparent drunkenness.

Conclusion

While D-lactic acidosis is considered a relatively rare disorder, mild or less severe cases may go undiagnosed. The possibility of D-lactic acidosis should be considered when any of the aforementioned neurologic or behavioral symptoms are observed. Proper diagnosis and therapies are essential in effectively treating and managing this problem.
Note: For a more complete review on the topic of D-lactic acidosis, see Petersen C, D-lactic acidosis. Nutr Clin Pract 2005; 20:634-645.

Craig Petersen, RD, CNSC, works part-time for Nutrishare. In addition to caring for consumers, his work there involves projects and investigations to reduce long-term complications and improve quality of life in the HPN consumer. He is retired from the University of California, Davis, Medical Center, where he spent a major portion of twenty-eight years also caring for HPN consumers. In his position there, he served on both pediatric and adult nutrition support teams, as well as the hospital nutrition committee. Craig has participated in and supported Oley Foundation activities for many years.

This website is an educational resource. It is not intended to provide medical advice or recommend a course of treatment. You should discuss all issues, ideas, suggestions, etc. with your clinician prior to use. Clinicians in a relevant field have reviewed the medical information; however, the Oley Foundation does not guarantee the accuracy of the information presented, and is not liable if information is incorrect or incomplete. If you have questions please contact Oley staff.

Updated in 2015 with a generous grant from Shire, Inc.

This website was updated in 2015 with a generous grant from Shire, Inc. This website is an educational resource. It is not intended to provide medical advice or recommend a course of treatment. You should discuss all issues, ideas, suggestions, etc. with your clinician prior to use. Clinicians in a relevant field have reviewed the medical information; however, the Oley Foundation does not guarantee the accuracy of the information presented, and is not liable if information is incorrect or incomplete. If you have questions please contact Oley staff.